469 research outputs found

    Interplay of nematic and magnetic orders in FeSe under pressure

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    We offer an explanation for the recently observed pressure-induced magnetic state in the iron-chalcogenide FeSe based on \textit{ab initio} estimates for the pressure evolution of the most important Coulomb interaction parameters. We find that an increase of pressure leads to an overall decrease mostly in the nearest-neighbor Coulomb repulsion, which in turn leads to a reduction of the nematic order and the generation of magnetic stripe order. We treat the concomitant effects of band renormalization and the induced interplay of nematic and magnetic order in a self-consistent way and determine the generic topology of the temperature-pressure phase diagram, and find qualitative agreement with the experimentally determined phase diagram.Comment: 13 pages, 6 fig

    Comparison of geodetic and geologic data from the Wasatch region, Utah, and implications for the spectral character of Earth deformation at periods of 10 to 10 million years

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    The Wasatch fault and adjacent fault zones provide an opportunity to compare present-day deformation rate estimates obtained from space geodesy with geologic displacement rates over at least four temporal windows, ranging from the last millennium up to 10 Myr. The three easternmost GPS sites of the Basin and Range Geodetic Network (BARGEN) at this latitude define a ∼130-km-wide region spanning three major normal faults extending east-west at a total rate of 2.7 ± 0.4 mm/yr, with an average regional strain rate estimated to be 21 ± 4 nstrain/yr, about twice the Basin and Range average. On the Wasatch fault, the vertical component of the geologic displacement rate is 1.7 ± 0.5 mm/yr since 6 ka, <0.6 mm/yr since 130 ka, and 0.5–0.7 mm/yr since 10 Ma. However, it appears likely that at the longest timescale, rates slowed over time, from 1.0 to 1.4 mm/yr between 10 and 6 Ma to 0.2 to 0.3 mm/yr since 6 Ma. The cumulative vertical displacement record across all three faults also shows time-variable strain release ranging from 2 to 4 mm/yr since 10 ka to <1 mm/yr averaged over the past 130 kyr. Conventional earthquake recurrence models (“Reid-type” behavior) would require an accordingly large variation in strain accumulation or loading rate on a 10-kyr timescale, for which there appears to be no obvious geophysical explanation. Alternatively, seismic strain release, given a wide range of plausible constitutive behaviors for frictional sliding, may be clustered on the 10-kyr timescale, resulting in the high Holocene rates, with comparatively low, uniform strain accumulation rates on the 100-kyr timescale (“Wallace-type” behavior). The latter alternative, combined with observations at the million-year timescale and the likelihood of a significant contribution of postseismic transients, implies maxima of spectral amplitude in the velocity field at periods of ∼10 Myr (variations in tectonic loading), ∼10 kyr (clustered strain release), and of 100 years (postseismic transients). If so, measurements of strain accumulation and strain release may be strongly timescale-dependent for any given fault system

    A Functional Role for ADAM10 in Human Immunodeficiency Virus Type-1 Replication

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    <p>Abstract</p> <p>Background</p> <p>Gene trap insertional mutagenesis was used as a high-throughput approach to discover cellular genes participating in viral infection by screening libraries of cells selected for survival from lytic infection with a variety of viruses. Cells harboring a disrupted <it>ADAM10 </it>(A Disintegrin and Metalloprotease 10) allele survived reovirus infection, and subsequently ADAM10 was shown by RNA interference to be important for replication of HIV-1.</p> <p>Results</p> <p>Silencing ADAM10 expression with small interfering RNA (siRNA) 48 hours before infection significantly inhibited HIV-1 replication in primary human monocyte-derived macrophages and in CD4<sup>+ </sup>cell lines. In agreement, ADAM10 over-expression significantly increased HIV-1 replication. ADAM10 down-regulation did not inhibit viral reverse transcription, indicating that viral entry and uncoating are also independent of ADAM10 expression. Integration of HIV-1 cDNA was reduced in ADAM10 down-regulated cells; however, concomitant 2-LTR circle formation was not detected, suggesting that HIV-1 does not enter the nucleus. Further, ADAM10 silencing inhibited downstream reporter gene expression and viral protein translation. Interestingly, we found that while the metalloprotease domain of ADAM10 is not required for HIV-1 replication, ADAM15 and γ-secretase (which proteolytically release the extracellular and intracellular domains of ADAM10 from the plasma membrane, respectively) do support productive infection.</p> <p>Conclusions</p> <p>We propose that ADAM10 facilitates replication at the level of nuclear trafficking. Collectively, our data support a model whereby ADAM10 is cleaved by ADAM15 and γ-secretase and that the ADAM10 intracellular domain directly facilitates HIV-1 nuclear trafficking. Thus, ADAM10 represents a novel cellular target class for development of antiretroviral drugs.</p

    An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses

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    Mycobacterium tuberculosis (M.tb) infection causes marked tissue inflammation leading to lung destruction and morbidity. The inflammatory extracellular microenvironment is acidic, however the effect of this acidosis on the immune response to M.tb is unknown. Using RNA-seq we show that acidosis produces system level transcriptional change in M.tb infected human macrophages regulating almost 4000 genes. Acidosis specifically upregulated extracellular matrix (ECM) degradation pathways with increased expression of Matrix metalloproteinases (MMPs) which mediate lung destruction in Tuberculosis. Macrophage MMP-1 and -3 secretion was increased by acidosis in a cellular model. Acidosis markedly suppresses several cytokines central to control of M.tb infection including TNF-α and IFN-γ. Murine studies demonstrated expression of known acidosis signaling G-protein coupled receptors OGR-1 and TDAG-8 in Tuberculosis which are shown to mediate the immune effects of decreased pH. Receptors were then demonstrated to be expressed in patients with TB lymphadenitis. Collectively, our findings show that an acidic microenvironment modulates immune function to reduce protective inflammatory responses and increase extracellular matrix degradation in Tuberculosis. Acidosis receptors are therefore potential targets for host directed therapy in patients

    Two-Loop Calculations with Vertex Corrections in the Walecka Model

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    Two-loop corrections with scalar and vector form factors are calculated for nuclear matter in the Walecka model. The on-shell form factors are derived from vertex corrections within the framework of the model and are highly damped at large spacelike momenta. The two-loop corrections are evaluated first by using the one-loop parameters and mean fields and then by refitting the total energy/baryon to empirical nuclear matter saturation properties. The modified two-loop corrections are significantly smaller than those computed with bare vertices. Contributions from the anomalous isoscalar form factor of the nucleon are included for the first time. The effects of the implicit density dependence of the form factors, which arise from the shift in the baryon mass, are also considered. Finally, necessary extensions of these calculations are discussed.Comment: 29 pages in REVTeX, 18 figures, preprint IU/NTC 94-02 //OSU--94-11

    Prescription of reninâ angiotensinâ aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care

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    Reninâ angiotensinâ aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66â 72 years; congestive heart failure [CHF] in 11%â 19%; diabetes in 43%â 54%; serum potassium â ¥5 in 20%â 35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong classâ specific recommendations. Although the reasons for this variation could not be fully identified in this crossâ sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150590/1/jch13563.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150590/2/jch13563_am.pd

    A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries

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    Genome targeting methods enable cost-effective capture of specific subsets of the genome for sequencing. We present here an automated, highly scalable method for carrying out the Solution Hybrid Selection capture approach that provides a dramatic increase in scale and throughput of sequence-ready libraries produced. Significant process improvements and a series of in-process quality control checkpoints are also added. These process improvements can also be used in a manual version of the protocol

    Can biodiversity of preexisting and created salt marshes match across scales? An assessment from microbes to predators

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    Coastal wetlands are rapidly disappearing worldwide due to a variety of processes, including climate change and flood control. The rate of loss in the Mississippi River Delta is among the highest in the world and billions of dollars have been allocated to build and restore coastal wetlands. A key question guiding assessment is whether created coastal salt marshes have similar biodiversity to preexisting, reference marshes. However, the numerous biodiversity metrics used to make these determinations are typically scale dependent and often conflicting. Here, we applied ecological theory to compare the diversity of different assemblages (surface and below-surface soil microbes, plants, macroinfauna, spiders, and on-marsh and off-marsh nekton) between two created marshes (4–6 years old) and four reference marshes. We also quantified the scale-dependent effects of species abundance distribution, aggregation, and density on richness differences and explored differences in species composition. Total, between-sample, and within-sample diversity (γ, β, and α, respectively) were not consistently lower at created marshes. Richness decomposition varied greatly among assemblages and marshes (e.g., soil microbes showed high equitability and α diversity, but plant diversity was restricted to a few dominant species with high aggregation). However, species abundance distribution, aggregation, and density patterns were not directly associated with differences between created and reference marshes. One exception was considerably lower density for macroinfauna at one of the created marshes, which was drier because of being at a higher elevation and having coarser substrate compared with the other marshes. The community compositions of created marshes were more dissimilar than reference marshes for microbe and macroinfauna assemblages. However, differences were small, particularly for microbes. Together, our results suggest generally similar taxonomic diversity and composition between created and reference marshes. This provides support for the creation of marsh habitat as tools for the maintenance and restoration of coastal biodiversity. However, caution is needed when creating marshes because specific building and restoration plans may lead to different colonization patterns
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